Nosocomial Sepsis in VLBW Neonates and Emergence of Antibiotic Resistance: An Epidemiological Study from the Spanish Neonatal Network “Grupo Castrillo”

Introduction: Nosocomial sepsis (NS) is a serious problem in very-low-birth-weight (VLBW) infants and a leading cause of neonatal morbidity and mortality. Their high frequency is related to the immaturity host defenses, frequent exposure to invasive diagnostic and treatment procedures, and prolonged hospital stay of these infants. The emergence of multiresistant bacteria is a serious problem in the management of these infections. The objective of this study was to assess the epidemiology of NS in VLBW infants in Spain.

Materials and Methods: Since 2006, NICUs and Neonatology Services of 40 Teaching hospitals in Spain form part of the so-called Neonatal Network “Grupo Castrillo,” whose mission is to carry out a prospective surveillance of the epidemiology of NS in VLBW infants in Spain. Here, we present the results obtained in the period 2006 to 2016.

Results: The network reported on 4,756 VLBW infants having a total of 6,100 episodes of sepsis occurring out of 20,935 admissions in the study period. The incidence rate of sepsis was 29.1%, ranging between 33.4% (2008) and 23.1% (2016). No significant differences were detected over the years. Around 80% of cases occurred in infants with a CVC in place, and almost half of the cases were defined as catheter-related sepsis according to the literature’s criteria. Some 65% of the episodes were caused by gram-positive bacteria, with the most common gram-positive isolate being S. epidermidis (49%). Gram-negative bacilli were responsible of 28% of cases with Klebsiella spp. (10.4%) as most common isolated pathogen. Candida spp. was isolated in 409 cases of NS (6.7%) with a significant decrease over the years of study (from 10.7 to 3.6%). The overall mortality rate was 11%, with a significant decrease over the years (from 15.8 to 6.4%) and with significant differences among pathogens. The most common initial empirical antibiotic therapy was a combination of vancomycin plus amikacin, being vancomycin the antibiotic mostly used as definitive treatment. As for what concerns the emergence of antibiotic resistance, 96% of the isolated S. epidermidis were resistant to oxacillin but despite the generalized use of vancomycin, no resistance was found during the study years. ESBL-producing Klebsiella spp. was documented in 143 of 512 blood cultures with antibiogram performed (27.9%) without significant variability throughout the studied period. Only seven cases of carbapenem-resistant Klebsiella spp. were documented.

Conclusion: (1) In our country, the incidence of NS in VLBW in the reported period was high, but similar to other recent series reported. (2) Gram-positive rods were the most commonly isolated pathogens; S. epidermidis caused 49% of NS. Klebsiella spp. was the most frequently isolated gram-negative bacillus. (3) The incidence of candidemia was lower than reported in other series and showed a significant decrease over the years, likely related to the concomitantly increasing use of fluconazole prophylaxis. (4) Vancomycin was the most commonly used antibiotic as definitive treatment. (5) The isolation of multiresistant bacteria stands as an emerging concern also in neonatal units.

Keywords: nosocomial sepsis, late-onset sepsis, very-low-birth-weight infants, antibiotic resistance, ESBL enterobacteriae